Unit

UNIT 6.16 Glutamate Cysteine Ligase (GCL) Transgenic and Gene-Targeted Mice for Controlling Glutathione Synthesis

  1. Isaac Mohar,
  2. Dianne Botta,
  3. Collin C. White,
  4. Lisa A. McConnachie,
  5. Terrance J. Kavanagh

Published Online: 1 FEB 2009

DOI: 10.1002/0471140856.tx0616s39

Current Protocols in Toxicology

Current Protocols in Toxicology

How to Cite

Mohar, I., Botta, D., White, C. C., McConnachie, L. A. and Kavanagh, T. J. 2009. Glutamate Cysteine Ligase (GCL) Transgenic and Gene-Targeted Mice for Controlling Glutathione Synthesis. Current Protocols in Toxicology. 39:6.16:6.16.1–6.16.20.

Author Information

  1. University of Washington, Seattle, Washington

Publication History

  1. Published Online: 1 FEB 2009
  2. Published Print: FEB 2009

Abstract

The tripeptide glutathione (GSH) has important antioxidant properties, scavenges free radicals, and serves as a cofactor for glutathione S-transferase conjugation of many xenobiotics. GSH is synthesized in two steps. The first and, often, rate-limiting step is the formation of γ-glutamylcysteine, which is catalyzed by the inducible heterodimeric enzyme glutamate cysteine ligase (GCL). The two subunits of GCL are the catalytic subunit (GCLC) and the modifier subunit (GCLM). In this unit, the generation and basic characterization methodologies of transgenic mouse models that have been developed to (1) conditionally over express both GCL subunits; (2) lack GCLM (Gclm null); and (3) create a hybrid between Gclm conditional over-expressing mice on a Gclm null genetic background are discussed. These models can be used to explore the fundamental role of GCLC and GCLM in GSH synthesis, as well as the toxicological role of GSH and its synthesis in xenobiotic metabolism and response to oxidative stress. Curr. Protoc. Toxicol. 39:6.16.1-6.16.20. © 2009 by John Wiley & Sons, Inc.

Keywords:

  • glutathione;
  • glutamate cysteine ligase;
  • oxidative stress;
  • transgenic mouse;
  • genetic model